The Cell Wall Polymer Lipoteichoic Acid Becomes Nonessential in Staphylococcus aureus Cells Lacking the ClpX Chaperone

Kristoffer T. Baek; Lisa Bowman; Charlotte Millership; Mia Dupont Sogaard; Volkhard Kaever; Pia Siljamaki; Kirsi Savijoki; Pekka Varmanen; Tuula A. Nyman; Angelika Grundling; Dorte Frees

doi:10.1128/mBio.01228-16

The Cell Wall Polymer Lipoteichoic Acid Becomes Nonessential in Staphylococcus aureus Cells Lacking the ClpX Chaperone

Kristoffer T. Baek, Lisa Bowman, Charlotte Millership, Mia Dupont Sogaard, Volkhard Kaever, Pia Siljamaki, Kirsi Savijoki, Pekka Varmanen, Tuula A. Nyman, Angelika Grundling, Dorte Frees

Food Safety and Zoonoses

17 Citations (Scopus)

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Abstract

Lipoteichoic acid (LTA) is an important cell wall component of Gram-positive bacteria and a promising target for the development of vaccines and antimicrobial compounds against Staphylococcus aureus. Here we demonstrate that mutations in the conditionally essential ltaS (LTA synthase) gene arise spontaneously in an S. aureus mutant lacking the ClpX chaperone. A wide variety of ltaS mutations were selected, and among these, a substantial portion resulted in premature stop codons and other changes predicted to abolish LtaS synthesis. Consistent with this assumption, the clpX ltaS double mutants did not produce LTA, and genetic analyses confirmed that LTA becomes nonessential in the absence of the ClpX chaperone. In fact, inactivation of ltaS alleviated the severe growth defect conferred by the clpX deletion. Microscopic analyses showed that the absence of ClpX partly alleviates the septum placement defects of an LTA-depleted strain, while other phenotypes typical of LTA-negative S. aureus mutants, including increased cell size and decreased autolytic activity, are retained. In conclusion, our results indicate that LTA has an essential role in septum placement that can be bypassed by inactivating the ClpX chaperone.

Original language	English
Article number	01228
Journal	mBio (Print)
Volume	7
Issue number	4
Number of pages	11
ISSN	2150-7511
DOIs	https://doi.org/10.1128/mBio.01228-16
Publication status	Published - 1 Jul 2016

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10.1128/mBio.01228-16Licence: CC BY

mBio-2016-Bæk-Final published version, 1.68 MBLicence: CC BY

Cite this

@article{e34d34f5c9934ab3898669257f9fdb20,

title = "The Cell Wall Polymer Lipoteichoic Acid Becomes Nonessential in Staphylococcus aureus Cells Lacking the ClpX Chaperone",

abstract = "Lipoteichoic acid (LTA) is an important cell wall component of Gram-positive bacteria and a promising target for the development of vaccines and antimicrobial compounds against Staphylococcus aureus. Here we demonstrate that mutations in the conditionally essential ltaS (LTA synthase) gene arise spontaneously in an S. aureus mutant lacking the ClpX chaperone. A wide variety of ltaS mutations were selected, and among these, a substantial portion resulted in premature stop codons and other changes predicted to abolish LtaS synthesis. Consistent with this assumption, the clpX ltaS double mutants did not produce LTA, and genetic analyses confirmed that LTA becomes nonessential in the absence of the ClpX chaperone. In fact, inactivation of ltaS alleviated the severe growth defect conferred by the clpX deletion. Microscopic analyses showed that the absence of ClpX partly alleviates the septum placement defects of an LTA-depleted strain, while other phenotypes typical of LTA-negative S. aureus mutants, including increased cell size and decreased autolytic activity, are retained. In conclusion, our results indicate that LTA has an essential role in septum placement that can be bypassed by inactivating the ClpX chaperone.",

author = "Baek, {Kristoffer T.} and Lisa Bowman and Charlotte Millership and Sogaard, {Mia Dupont} and Volkhard Kaever and Pia Siljamaki and Kirsi Savijoki and Pekka Varmanen and Nyman, {Tuula A.} and Angelika Grundling and Dorte Frees",

year = "2016",

month = jul,

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doi = "10.1128/mBio.01228-16",

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T1 - The Cell Wall Polymer Lipoteichoic Acid Becomes Nonessential in Staphylococcus aureus Cells Lacking the ClpX Chaperone

AU - Baek, Kristoffer T.

AU - Bowman, Lisa

AU - Millership, Charlotte

AU - Sogaard, Mia Dupont

AU - Kaever, Volkhard

AU - Siljamaki, Pia

AU - Savijoki, Kirsi

AU - Varmanen, Pekka

AU - Nyman, Tuula A.

AU - Grundling, Angelika

AU - Frees, Dorte

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Lipoteichoic acid (LTA) is an important cell wall component of Gram-positive bacteria and a promising target for the development of vaccines and antimicrobial compounds against Staphylococcus aureus. Here we demonstrate that mutations in the conditionally essential ltaS (LTA synthase) gene arise spontaneously in an S. aureus mutant lacking the ClpX chaperone. A wide variety of ltaS mutations were selected, and among these, a substantial portion resulted in premature stop codons and other changes predicted to abolish LtaS synthesis. Consistent with this assumption, the clpX ltaS double mutants did not produce LTA, and genetic analyses confirmed that LTA becomes nonessential in the absence of the ClpX chaperone. In fact, inactivation of ltaS alleviated the severe growth defect conferred by the clpX deletion. Microscopic analyses showed that the absence of ClpX partly alleviates the septum placement defects of an LTA-depleted strain, while other phenotypes typical of LTA-negative S. aureus mutants, including increased cell size and decreased autolytic activity, are retained. In conclusion, our results indicate that LTA has an essential role in septum placement that can be bypassed by inactivating the ClpX chaperone.

AB - Lipoteichoic acid (LTA) is an important cell wall component of Gram-positive bacteria and a promising target for the development of vaccines and antimicrobial compounds against Staphylococcus aureus. Here we demonstrate that mutations in the conditionally essential ltaS (LTA synthase) gene arise spontaneously in an S. aureus mutant lacking the ClpX chaperone. A wide variety of ltaS mutations were selected, and among these, a substantial portion resulted in premature stop codons and other changes predicted to abolish LtaS synthesis. Consistent with this assumption, the clpX ltaS double mutants did not produce LTA, and genetic analyses confirmed that LTA becomes nonessential in the absence of the ClpX chaperone. In fact, inactivation of ltaS alleviated the severe growth defect conferred by the clpX deletion. Microscopic analyses showed that the absence of ClpX partly alleviates the septum placement defects of an LTA-depleted strain, while other phenotypes typical of LTA-negative S. aureus mutants, including increased cell size and decreased autolytic activity, are retained. In conclusion, our results indicate that LTA has an essential role in septum placement that can be bypassed by inactivating the ClpX chaperone.

U2 - 10.1128/mBio.01228-16

DO - 10.1128/mBio.01228-16

M3 - Journal article

C2 - 27507828

SN - 2161-2129

VL - 7

JO - mBio

JF - mBio

IS - 4

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